It is proposed to continue studies of the mechanism of enzymatic dechlorination in rat and human tissue. Recent studies of this subject have indicated that the enzyme system in rats is the microsomal mixed function oxygenase and by isolating and recombining cytochrome P-450 and NADPH cytochrome c reductase and adding NADPH and a phospholipid, enzymatic dechlorinating activity was obtained. We plan to extend this to human liver tissue in an attempt to determine the characteristics of human hepatic mixed function oxygenase and its ability to carry out dechlorination. The dechlorination reaction as carried out by the mixed function oxygenase system is oxidative. However, we have found that in the absence of oxygen this system alters halogenated compounds. We propose to study this to determine if this alteration represents a reductive dechlorination and if this reaction may contribute to the toxicity often related to chlorinated compounds. In addition to studying the dechlorination reaction in hepatic tissue, studies will also be conducted in lung tissue. These studies will be carried out in an isolated perfused lung preparation from rats and rabbits and in vitro in lung microsomes prepared from either rat, rabbit, or human lung samples. Substrates for these studies have included halothane and 1,1,2,-trichloroethane, each labeled with either 14C or 36Cl. We plan to continue using these as substrates and to use other chlorinated compounds with the choice dictated by importance to human health and availability with radioisotope labeling. BIBLIOGRAPHIC REFERENCES: Tinker, J. H., Gandolfi, A. J., Van Dyke, R. A.: Elevation of Plasma Bromide Levels in Patients Following Halothane Anesthesia: Time Correlation with Total Halothane Dosage. Anesthesiology 44: 194-196, 1976. Widger, L. A., Gandolfi, A. J., Van Dyke, R. A.: Hypoxic and Halothane Metabolism In Vivo Release of Inorganic Fluoride and Halothane Metabolite Binding to Cellular Constituents. Anesthesiology 44:197-201, 1976.